The US Food and Drug Administration (FDA) has approved flortaucipir F18 injection (Tauvid, Avid Radiopharmaceuticals), a diagnostic agent for adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD). The tau radiotracer for is injected into a vein in preparation for the imaging test, positron emission tomography (PET) scan to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in the brain.
The approval was based on findings from two clinical trials. The open-label phase III study, A16, examined 156 patients with dementia, mild cognitive impairment, or normal cognition. All patients were terminally ill and consented to donate their brain for evaluation in an autopsy following their deaths. Analysis of 64 patients met pre-specified success criteria and the flortaucipir PET scans were evaluated by 5 readers who were blinded to clinical and neuropathological results. Analyses included assessment of an AD tau patterns of flortaucipir retention was assessed for correspondence with both a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-ß plaques sufficient to meet the criteria for high levels of ADNC. Results demonstrating B3 level NFTs sensitivity was 89.1% (95% CI, 77.0–95.3) and specificity was 86.1% (95% CI, 71.3–93.9), and high ADNC level sensitivity was 95.1% (95% CI, 83.9–98.7) and specificity was 82.9% (95% CI, 68.7–91.5). A second phase III study included the same terminally ill patients as in A16, plus 18 additional terminally ill patient, and 159 patients with cognitive impairment being evaluated for AD. An inter-reader agreement was evaluated using Fleiss' kappa statistic and found to be 0.87 (95% CI: 0.83, 0.91) across 241 patients. The most common adverse reactions reported in clinical trials were headache (1.4%), injection site pain (1.2%), and increased blood pressure (0.8%).
Illustrative example of radioligands that bind to tau and are visualized using PET
The FDA notes that the ability of flortaucipir F18 PET scans to detect tau pathology was assessed in patients with generally severe stages of dementia and may be lower in patients with cognitive decline of earlier stages.
>> FDA Press Release
Fleisher AS et al. JAMA Neurol. 2020; Epub ahead of print. Abstract
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